RESUMEN
Traumatic brain injury is an increasingly common public health issue, with the mild variant most clinically relevant for this chapter. Common causes of mild traumatic brain injury (mTBI) include motor vehicle accidents, athletics, and military training/deployment. Despite a range of clinically available testing platforms, diagnosis of mTBI remains challenging. Symptoms are primarily neurosensory, and include dizziness, hearing problems, headaches, cognitive, and sleep disturbances. Dizziness is nearly universally present in all mTBI patients, and is the easiest symptom to objectify for diagnosis. Aside from a thorough history and physical exam, in the near future specialized vestibular function tests will be key to mTBI diagnosis. A battery of oculomotor (antisaccade, predictive saccade) and vestibular tasks (head impulse test) has been demonstrated to sensitively and specifically identify individuals with acute mTBI. Vestibular therapy and rehabilitation have shown improvements for mTBI patients in cognitive function, ability to return to activities of daily living, and ability to return to work. Dizziness, as a contributor to short- and long-term disability following mTBI, is ultimately crucial not only for diagnosis but also for treatment.
Asunto(s)
Lesiones Traumáticas del Encéfalo/complicaciones , Mareo/etiología , Vértigo/etiología , Mareo/diagnóstico , Medidas del Movimiento Ocular , Humanos , Vértigo/diagnóstico , Pruebas de Función VestibularRESUMEN
Transtympanic gentamicin is becoming increasingly popular in the treatment of Meniere's disease. In this report we examine our experience with the use of microdose gentamicin via the Round Window Microcatheter for the treatment of Meniere's disease. Thirty-six patients were treated with gentamicin administration via the Round Window Microcatheter between July 1997 and August 2000. The patients all underwent 10 days of continuous treatment with a total dose of 2.4-3.75 mg of gentamicin (10 mg/ml). All patients had extensive pre-, intra-, and post-therapy auditory and vestibular testing. In this group, vertigo was eliminated in 89% of the patients, and tinnitus and pressure were significantly reduced in over 60% of the patients. Only one patient suffered a significant hearing loss and, most importantly, in all but one patient vestibular function was improved or normalized after treatment. Round Window Microcatheter-administered microdose gentamicin is an exciting new treatment for Meniere's disease. Preliminary results indicate that vertigo can be controlled without a significant reduction in cochlear or vestibular function in most patients. These results suggest that this therapy may be acting at a non-hair cell site. Our results are compared to the published literature examining transtympanic injection. In addition, the underlying science supporting this type of treatment is examined.
Asunto(s)
Gentamicinas/administración & dosificación , Enfermedad de Meniere/tratamiento farmacológico , Ventana Redonda , Adulto , Anciano , Audiometría , Audiometría de Respuesta Evocada , Cateterismo , Femenino , Gentamicinas/uso terapéutico , Humanos , Masculino , Enfermedad de Meniere/fisiopatología , Persona de Mediana Edad , Postura , Resultado del Tratamiento , Vértigo/tratamiento farmacológico , Pruebas de VisiónRESUMEN
The effects of a combination of two antioxidant compounds were studied in a chinchilla model of noise-induced hearing loss. After obtaining baseline hearing thresholds using inferior colliculus evoked potentials, chinchillas were exposed for 6 h to octave band noise centered at 4 kHz (105 dB SPL). Post-noise thresholds were obtained 1 h after the noise exposure, and then animals received either saline or salicylate and N-L-acetylcysteine combination. Another group received antioxidant treatment 1 h prior to noise. Hearing was tested at 1, 2 and 3 weeks post-noise. Subsequently, the cochleae were harvested, and cytocochleograms were prepared. There was a 20-40 dB SPL threshold shift at 3 weeks for tested controls. Permanent threshold shifts (PTS) were significantly reduced (P<0.05) to approximately 10 dB for the pre-treatment group at week 3. The PTS for the post-treatment group at week 3 was similar to the pre-treatment group at 1 and 2 kHz (0-10 dB) but was intermediate between the control and pre-treatment groups at 4 and 8 kHz (23 dB). Animals pre-treated with antioxidant had a significant reduction in hair cell loss but those post-treated with antioxidant had no protection from hair cell loss. These findings demonstrate the feasibility of reduction of noise-induced hearing loss using clinically available antioxidant compounds.
Asunto(s)
Acetilcisteína/uso terapéutico , Pérdida Auditiva Provocada por Ruido/tratamiento farmacológico , Salicilatos/uso terapéutico , Animales , Audiometría , Umbral Auditivo/efectos de los fármacos , Recuento de Células , Chinchilla , Combinación de Medicamentos , Células Ciliadas Auditivas/efectos de los fármacos , Células Ciliadas Auditivas/patología , Pérdida Auditiva Provocada por Ruido/fisiopatologíaRESUMEN
Injury to the internal carotid artery during procedures performed in the tonsillar fossa can be catastrophic. Tonsillectomy or uvulopalatopharyngoplasty was performed on 32 patients at the Hospital of the University of Pennsylvania or the Children's Hospital of Philadelphia. Using Doppler ultrasonography, the course of the internal carotid artery in the postsurgical tonsillar fossa was mapped. The results indicate that, in the majority of patients, the internal carotid artery is located between 20% and 60% of the total width across the tonsillar fossa, as measured from the posterior pillar. Appreciation of the surgical anatomy of the tonsillar fossa with respect to the internal carotid artery should contribute to improved intraoperative judgment and further limit the risk of vascular injury during oropharyngeal procedures.
Asunto(s)
Arteria Carótida Interna/anatomía & histología , Tonsilectomía , Ultrasonografía , Adolescente , Adulto , Velocidad del Flujo Sanguíneo , Femenino , Humanos , Cuidados Intraoperatorios , Complicaciones Intraoperatorias/prevención & control , Masculino , Persona de Mediana Edad , UltrasonidoRESUMEN
OBJECTIVES/HYPOTHESIS: Transtympanic gentamicin is an increasingly popular treatment for Meniere's disease. The present report examines the 2-year follow-up of our first 27 patients with Meniere's disease treated with the use of microdose gentamicin through the Round Window Microcatheter. We applied the 1995 American Academy of Otolaryngology-Head and Neck Surgery criteria to this patient group to analyze the results of treatment. STUDY DESIGN: This study is an evaluation of consecutive patients with predetermined data collection on each patient. METHODS: Patients with confirmed Meniere's disease underwent placement of the Round Window Microcatheter, which was filled with 10 mg/mL gentamicin, after placement into the round window niche was confirmed. Ten milligrams per milliliter of gentamicin was injected into the catheter by hand on two occasions after device placement in the first several patients. The remaining patients had continuous infusion of 10 mg/mL gentamicin at 1microL/h for the next 10 days. The catheter was removed 10 days after placement. All patients underwent an extensive set of hearing and vestibular tests on several occasions before, during, and after treatment. RESULTS: In the patients in the study, vertigo was eliminated in 92.6%, with 3.7% of patients (1/27) demonstrating a mild permanent threshold shift in hearing. Tinnitus and pressure were significantly reduced in more than 65% of patients. Only one patient demonstrated a reduction of vestibular function after treatment. CONCLUSIONS: Results of this study on this group of patients indicate that vertigo can be controlled in the long term using microdose gentamicin without a significant reduction in cochlear or vestibular function in most of the patients in our series. Our results are compared with the published literature examining transtympanic injection. In addition, the underlying science supporting this type of treatment is examined.
Asunto(s)
Antibacterianos/administración & dosificación , Sistemas de Liberación de Medicamentos/instrumentación , Gentamicinas/administración & dosificación , Enfermedad de Meniere/tratamiento farmacológico , Ventana Redonda , Adulto , Antibacterianos/uso terapéutico , Catéteres de Permanencia , Femenino , Estudios de Seguimiento , Gentamicinas/uso terapéutico , Humanos , Masculino , Factores de TiempoRESUMEN
OBJECTIVES/HYPOTHESIS: Transtympanic gentamicin therapy has become a popular treatment modality for Meniere's disease, but questions regarding the ideal dose of medicine, the best administration paradigm, and the safest treatment end-point remain unanswered. The goal of this study is to examine the inner ear kinetics of transtympanic gentamicin and compare this with the kinetics of sustained-release delivery in a basic science model. In addition, we plan to examine the relationship of these kinetics curves to the effect of the two treatment modalities on inner ear function and morphology. It is hoped that this analysis will help clinicians to better apply local medical therapy to the ear. STUDY DESIGN: The study is a basic science project designed to examine perilymph gentamicin concentrations, hearing results, and inner ear morphology in an animal model. METHODS: Gentamicin was applied to the right ear of chinchillas either through a transtympanic approach or in a sustained-release device. The left ear remained untreated as an internal control. At set time points the animals' hearing and balance function was studied and the perilymph was harvested, after which the animal was killed and preserved for histological evaluation. Kinetics curves were constructed for each of the two treatment paradigms and compared with histological and functional outcomes. RESULTS: The two groups yielded dramatically different kinetics curves. The transtympanic curve had a high peak level at 24 hours with rapid fall-off and almost total elimination by 48 hours, whereas the sustained-release curve was characterized by a long, flat plateau phase with a peak that was approximately one-third that of the transtympanic curve. In addition, the variability seen in perilymph concentrations was significantly higher in the transtympanic group than in the sustained-release group. Immunohistochemical analysis using antibodies against cleaved caspase-3 and cleaved caspase-7 demonstrated early damage in the spiral ganglion of both groups, before any obvious morphological change in the hair cells. The staining was significantly more dense in animals with transtympanic delivery. Cochlear and vestibular hair cell damage was seen at late time points in animals from both groups. Hearing loss (HL) progressed in an orderly fashion in the sustained-release group of animals, with no HL seen in the early time points and universal significant threshold shifts present by 72 hours. In the transtympanic group, the HL was more variable, with significant threshold shifts occurring as early as 4 hours after treatment, but with some animals demonstrating preserved hearing at the 72-hour time point. All animals demonstrated profound HL at the 6-day time point. CONCLUSIONS: There is a significant difference in the shape and variability of the perilymph kinetics curve when comparing sustained-release delivery to transtympanic delivery of gentamicin. High early peak levels of gentamicin seen with transtympanic therapy may have a profound effect on the spiral ganglion and produce early HL before obvious hair cell damage. Sustained delivery of gentamicin produces universal HL at 72 hours. The reliability of sustained-release delivery to the ear reduces functional and morphological variations between animals.
Asunto(s)
Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Gentamicinas/administración & dosificación , Gentamicinas/farmacocinética , Animales , Antibacterianos/efectos adversos , Audiometría , Chinchilla , Preparaciones de Acción Retardada , Oído Medio/efectos de los fármacos , Femenino , Inmunoensayo de Polarización Fluorescente , Gentamicinas/efectos adversos , Pérdida Auditiva/inducido químicamente , Inmunohistoquímica , Inyecciones Intralesiones , Modelos Animales , Órgano Espiral/efectos de los fármacos , PerilinfaRESUMEN
Congenital tracheal stenosis is a rare congenital anomaly, with less than 70 reported cases in the literature. The presenting signs and symptoms of stridor, recurrent pneumonia, and respiratory distress are commonly seen in other conditions. The rarity of congenital tracheal stenosis and the diverse presentations make accurate early diagnosis difficult and frequently lead to inappropriate treatment. We treated three patients with congenital tracheal stenosis who presented with different sites of stenosis. Each patient displayed different symptoms and required individualized management. The treatment of congenital tracheal stenosis depends on identifying the site and extent of the stenosis. We reviewed the embryogenesis and treatment of this abnormality and developed a new classification system that will aid in the management of congenital tracheal stenosis.
Asunto(s)
Estenosis Traqueal/congénito , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estenosis Traqueal/diagnóstico , Estenosis Traqueal/terapiaRESUMEN
Adenotonsillectomy is generally safe surgery, but surgeons should be cognizant of potential complications and be prepared to manage them. Postoperative hemorrhage usually responds to local measures or cautery but can be life-threatening. Preoperative screening of coagulation profiles appears unnecessary. Anesthetic risks have declined with modern techniques, but airway risks, aspiration, and pulmonary edema are possible. Nasopharyngeal valving may be altered by velopharyngeal incompetence or nasopharyngeal stenosis. Sore throat, otalgia, fever, dehydration, and uvular edema are more common postoperative complaints. Less common complications include atlantoaxial subluxation, mandible condyle fracture, infection, eustachian tube injury, and psychological trauma. The prevalence, management, and strategies for avoidance of these are discussed.
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Adenoidectomía , Complicaciones Posoperatorias , Tonsilectomía , Adenoidectomía/efectos adversos , Anestesia , Humanos , Complicaciones Posoperatorias/prevención & control , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/prevención & control , Cuidados Preoperatorios , Tonsilectomía/efectos adversosRESUMEN
A 2-year prospective double-blind study was performed to evaluate the role of etidronate disodium for the treatment of progressive hearing loss in patients with otosclerosis. A pulsed dosage regimen was used during the 2-year period and the patients were followed up with otologic and audiometric examinations. Although statistically significant differences were not achieved between the study and control groups, the study did reveal a trend toward stabilization or improvement in air conduction thresholds in some frequencies (1000 and 4000 Hz) and in bone conduction thresholds at other frequencies (500, 1000, and 2000 Hz). The incidence of adverse side effects was similar in the treatment and control groups. Although no definite conclusions can be drawn from this pilot study, the findings provide encouragement for performing a larger and longer-term study.
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Ácido Etidrónico/uso terapéutico , Pérdida Auditiva Conductiva/prevención & control , Pérdida Auditiva Sensorineural/prevención & control , Otosclerosis/tratamiento farmacológico , Adulto , Anciano , Umbral Auditivo/efectos de los fármacos , Método Doble Ciego , Ácido Etidrónico/efectos adversos , Femenino , Pérdida Auditiva Bilateral/etiología , Pérdida Auditiva Bilateral/prevención & control , Pérdida Auditiva Conductiva/etiología , Pérdida Auditiva Sensorineural/etiología , Humanos , Masculino , Persona de Mediana Edad , Otosclerosis/complicaciones , Proyectos Piloto , Estudios Prospectivos , Resultado del TratamientoRESUMEN
The effect of posterior fossa vestibular neurectomy on postoperative hearing levels of 172 patients was studied at 1 week, 1 month, 1 year, and 18 to 24 months. According to the 1985 American Academy of Otolaryngology-Head and Neck Surgery guidelines for reporting treatment outcome, 66% of patients had improved or unchanged hearing at 18 to 24 months. One-week postoperative hearing was poorer than at 1 month or later follow-up. Permanent profound hearing loss occurred in 4.7% of patients. In patients who had worse than 80 dB pure-tone average and 20% speech discrimination score hearing loss before surgery, 68% improved above this hearing level, and 16% improved to better than 50 dB pure-tone average and 50% speech discrimination after surgery. This suggests that it may be worthwhile to preserve the cochlear nerve in certain patients who may otherwise be candidates for labyrinthectomy. These hearing results are comparable with other treatment modalities including endolymphatic sac surgery.
Asunto(s)
Audición , Enfermedad de Meniere/cirugía , Nervio Vestibular/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Audiometría de Tonos Puros , Nervio Coclear/anatomía & histología , Nervio Coclear/cirugía , Sordera/etiología , Sordera/cirugía , Oído Interno/cirugía , Saco Endolinfático/cirugía , Estudios de Seguimiento , Guías como Asunto , Humanos , Persona de Mediana Edad , Percepción del Habla , Resultado del TratamientoRESUMEN
OBJECTIVE: To treat patients with sudden sensorineural hearing loss (SSNL) who failed oral prednisone therapy by using a round window membrane (RWM) microcatheter. This topical delivery strategy sought to improve effectiveness of steroid treatment to the inner ear by targeting drug delivery to the RWM. STUDY DESIGN: Nonrandomized prospective design. SETTING: Tertiary care facility. PATIENTS: Six patients with severe unilateral SSHL, five of whom were refractory to a course of oral steroid therapy treated within 6 weeks of SSHL and three additional patients treated more than 6 weeks after SSHL. INTERVENTION: Therapeutic use of RWM catheter. MAIN OUTCOME MEASURES: Pure-tone averages (PTAs) and word identification scores (WIS). RESULTS: Five of the six patients treated within 6 weeks of SSHL improved their WIS. Of the six, four returned to baseline hearing, one recovered hearing that could benefit by hearing amplification, and one regained moderate improvement in PTA but not WIS. CONCLUSION: Targeted topical steroid administration avoids the significant systemic side effects of oral steroids and may offer more effective dosing than simple transtympanic injection of medicine. Although these findings are preliminary, it is possible that after further study, targeted drug delivery may be a useful technique to consider in patients with severe to profound hearing loss that have failed all other management options.
Asunto(s)
Antiinflamatorios/uso terapéutico , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Administración Tópica , Adolescente , Anciano , Antiinflamatorios/administración & dosificación , Audiometría de Tonos Puros , Pérdida Auditiva Sensorineural/diagnóstico , Humanos , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Estudios Prospectivos , Ventana Redonda , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
The search for a safe, effective treatment for the vertigo associated with Meniere's disease has long been an important topic in otolaryngology. In recent years many groups have begun using intratympanic gentamicin to treat this vertigo. Although reported cure rates are as high as 90%, many questions remain regarding this type of treatment. Current limitations are the necessity for repeated treatments and a lack of clear dosing guidelines. In addition, the gentamicin must be delivered in a manner that allows maximal vestibulotoxic effect without injury to hearing. Until investigators can control the exact amount of medicine that is placed in the ear and have an understanding of the kinetics of gentamicin absorption, adequate dosing guidelines will be difficult to establish, and therapy will continue to rely on empiric data. We describe the use of a fibrin-based sustained-release vehicle, impregnated with gentamicin, injected into the middle ear of chinchillas. This allows for a prolonged effect without repeated dosing. Using this model, we studied the absorption kinetics of gentamicin at time points ranging from 8 hours to 1 week after injection. We used our findings to create a kinetics curve of gentamicin absorption. We discuss the shape and characteristics of this kinetics curve and examine the effects of the fibrin-based sustained-release vehicle and gentamicin on the middle ear. We noted no absorption in the contralateral (untreated ear) or blood. Through better understanding of the actions of gentamicin in this animal model, we hope to facilitate safer use of intratympanic medicines in our patient population and initiate programs for the use of this sustained-release vehicle in human beings.
Asunto(s)
Gentamicinas/administración & dosificación , Gentamicinas/farmacocinética , Perilinfa/metabolismo , Animales , Chinchilla , Preparaciones de Acción Retardada , Oído Interno/metabolismo , Oído Medio , Femenino , Adhesivo de Tejido de Fibrina , Inyecciones , MasculinoRESUMEN
The use of transtympanic gentamicin has become a popular method of treating Meniere's disease; nevertheless, many questions still remain regarding this therapy. Until investigators can control the exact amount of medicine that is administered to the ear and have an understanding of the kinetics of gentamicin, therapy will continue to rely on empirical data. Previously we described the use of a fibrin-based sustained-release vehicle impregnated with gentamicin in the middle ears of chinchillas. With this model a kinetics curve of gentamicin was defined. The inner ears of these animals were submitted for immunohistochemical and histologic analysis. We discuss the ultrastructural changes seen and correlate this to our kinetics data. We also examine measurement of hair cell damage with heat shock protein levels. By better understanding the actions of gentamicin in this animal model, we hope to facilitate safer use of intratympanic medicines in our patient population.
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Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Oído Interno/efectos de los fármacos , Oído Interno/ultraestructura , Gentamicinas/administración & dosificación , Gentamicinas/efectos adversos , Animales , Antibacterianos/farmacocinética , Chinchilla , Preparaciones de Acción Retardada , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Gentamicinas/farmacocinética , Células Ciliadas Auditivas/efectos de los fármacos , Células Ciliadas Auditivas/ultraestructura , Proteínas de Choque Térmico/análisis , Inmunohistoquímica , Instilación de Medicamentos , Masculino , Enfermedad de Meniere/tratamiento farmacológico , Factores de TiempoRESUMEN
Over the years, a variety of empirical regimens have evolved using intratympanic gentamicin to treat the vertigo associated with Meniere's disease. Although these regimens have been effective, their application is not without risk. Many of the problems associated with intratympanic medications could be overcome with the use of a sustained release vehicle. This article examines the role of such vehicles in the treatment of Meniere's disease and how sustained release vehicles might impact future treatment for this disabling disease.
Asunto(s)
Enfermedad de Meniere/terapia , Aminoglicósidos , Antibacterianos/uso terapéutico , Adhesivo de Tejido de Fibrina/uso terapéutico , Humanos , Factores de TiempoRESUMEN
Chondrosarcoma of the larynx is a rare malignancy accounting for 0.5% of all laryngeal tumors. We report our approach to laryngeal chondrosarcoma and review the recent literature on the subject. Our review supports the previously held opinions about sites of origin, but draws new conclusions about symptoms. In addition, we examine the controversy of conservative surgery vs. total laryngectomy.
Asunto(s)
Condrosarcoma , Neoplasias Laríngeas , Anciano , Anciano de 80 o más Años , Condrosarcoma/diagnóstico , Condrosarcoma/cirugía , Femenino , Humanos , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/cirugía , MasculinoAsunto(s)
Aneurisma/cirugía , Arteria Basilar/cirugía , Adulto , Arterias/cirugía , Seno Cavernoso , Cerebelo/irrigación sanguínea , Duramadre/irrigación sanguínea , Oído Interno , Femenino , Humanos , Venas Yugulares , Masculino , Apófisis Mastoides/cirugía , Métodos , Persona de Mediana Edad , Osteotomía/métodos , Arteria Vertebral/cirugíaRESUMEN
BACKGROUND: In this study, we review the results of Menière's disease treatment using microdose gentamycin delivered directly to the round window using a new microcatheter system. PATIENTS AND METHODS: 11 patients were treated by 1.25 mg gentamycin on the 3rd and 7th day after insertion of the new microcatheter at the niche of the round window membrane, while a second group of 7 patients was treated by a gentamycin dosage of 1 microliter/h continuously applied by a minipump over a period of 10 days. Electrocochleography was derived by an integrated electrode and the microcatheter was removed after 10 days. The results were analysed with a follow-up ranging from 6 to 12 months. RESULTS: In 15 of 18 patients (83%) tinnitus was improved significantly throughout the follow-up period. Vertigo was eliminated in all patients, and pressure was relieved in 17 of 18 (94%). CONCLUSIONS: These preliminary data suggest that gentamycin delivered by the Round-Window-Microcatheter is a safe and effective treatment for the reduction of tinnitus, vertigo, and pressure associated with Menière's disease.
Asunto(s)
Gentamicinas/administración & dosificación , Enfermedad de Meniere/tratamiento farmacológico , Acúfeno/tratamiento farmacológico , Audiometría de Respuesta Evocada , Cateterismo , Estudios de Seguimiento , Humanos , Bombas de Infusión , Enfermedad de Meniere/complicaciones , Ventana Redonda , Factores de Tiempo , Acúfeno/etiologíaRESUMEN
Advances in the field of skull base surgery have dramatically reduced the mortality and morbidity of operations on the skull base. Nevertheless, cerebral ischemic events from compromised blood supply to areas of the brain still occur. Although arterial compromise is responsible for a majority of these events, the venous side of the circulation can also play a role in producing cerebral infarctions. A key area of cerebral venous drainage is at the junction of the transverse sinus, sigmoid sinus, and vein of Labbé. Absence of the transverse sinus with the outflow of the vein of Labbé limited to the sigmoid sinus puts these patients at an increased risk for venous infarcts when this area is manipulated during skull base surgery. We have studied 100 consecutive carotid angiograms performed on 50 individuals for carotid artery disease or to rule out aneurysms. We have found that 16.7% of individuals have one atretic transverse sinus. We discuss our results and the implications that they have in skull base surgery. It is our hope that a better understanding of the cerebral venous drainage patterns will help skull base surgeons avoid complications in the future.
RESUMEN
Morbidity and mortality from acute coronary artery occlusion may be reduced if local myocardial adenosine concentration is augmented because 1) coronary collateral blood flow during ischemia increases with adenosine infusion, and 2) granulocytes that accumulate in the microcirculation during ischemia are, to a large extent, inhibited by adenosine from generating superoxide anion free radicals, from adhering to vascular endothelium, and from damaging endothelial cells in culture. Using a cultured lymphoblast model system, we found that 5-amino-4-imidazole carboxamide (AICA) riboside enhanced adenosine accumulation during ATP catabolism. Therefore, AICA riboside pretreatment was used in canine myocardium to selectively increase adenosine concentration in the ischemic area during 1 hour of ischemia. At 5 minutes of ischemia, endocardial flow to ischemic myocardium in saline-treated and AICA riboside-treated dogs was 0.06 +/- 0.03 and 0.34 +/- 0.11 ml/min/g, respectively (p less than 0.01); flow to nonischemic myocardium was not affected. Ventricular tachycardia and premature ventricular depolarizations were significantly attenuated in the AICA riboside-treated dogs. Blood pressure and heart rate were not affected by AICA riboside. In venous blood from ischemic tissue, adenosine increased from undetectable levels (less than 0.01 microM) to 0.22 +/- 0.08 microM in saline and 1.79 +/- 0.06 microM in AICA riboside-treated dogs, respectively (p less than 0.001). Coronary vein inosine concentrations were greater in saline than in AICA riboside-treated dogs. In separate in vitro studies, AICA riboside did not alter the removal rate of adenosine from canine blood. Indium-labeled granulocyte accumulation was significantly less in ischemic myocardium in AICA riboside-treated compared with saline-treated dogs. In addition, adenosine, but not AICA riboside, inhibited in vitro canine granulocyte superoxide production. We conclude that AICA riboside given before myocardial ischemia augments adenosine concentration, decreases arrhythmias, decreases granulocyte accumulation, and improves collateral flow to ischemic myocardium. One of the beneficial mechanisms could be an increased production of adenosine rather than inosine from ATP catabolism that causes vasodilation and inhibition of granulocytes. We propose a new hypothesis regarding regulation of the inflammatory reaction to ischemia in the microcirculation. Adenosine, in addition to its vasodilator action, is an anti-injury autacoid that links ATP catabolism to inhibition of granulocyte adherence, microvascular obstruction, and superoxide anion formation.
Asunto(s)
Adenosina/sangre , Aminoimidazol Carboxamida/uso terapéutico , Circulación Coronaria/efectos de los fármacos , Imidazoles/uso terapéutico , Daño por Reperfusión Miocárdica/prevención & control , Ribonucleósidos/uso terapéutico , Adenosina Trifosfato/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Animales , Células Cultivadas , Circulación Colateral/efectos de los fármacos , Perros , Granulocitos/efectos de los fármacos , Técnicas In Vitro , Miocardio/metabolismo , Superóxidos/metabolismoRESUMEN
The vestibules of adult guinea pigs were lesioned with gentamicin and then treated with perilymphatic infusion of either of two growth factor mixtures (i.e., GF I or GF II). GF I contained transforming growth factor alpha (TGFalpha), insulin-like growth factor type one (IGF-1), and retinoic acid (RA), whereas GF II contained those three factors and brain-derived neurotrophic factor. Treatment with GF I significantly enhanced vestibular hair cell renewal in ototoxin-damaged utricles and the maturation of stereociliary bundle morphology. The addition of brain-derived neurotrophic factor to the GF II infusion mixture resulted in the return of type 1 vestibular hair cells in ototoxin-damaged cristae, and improved vestibular function. These results suggest that growth factor therapy may be an effective treatment for balance disorders that are the result of hair cell dysfunction and/or loss.